Comic-Con issues a mask mandate, not the costume kind, for next week’s event in San Diego.

Federal officials have also warned that as the highly transmissible Omicron subvariant known as BA.5 fuels a new wave of infections, reinfections and hospitalizations, Americans must do more to protect themselves against the coronavirus, including wearing masks.

Before the pandemic, Comic-Con International annually drew tens of thousands of fans of fantasy comics, films and video games to San Diego. But in 2020, organizers made the “emotional” decision to cancel the event, Mr. Glanzer said.

It was moved online, and participants were able to watch recorded panels on YouTube. Since then, the organization has held two smaller in-person events, the Comic-Con Special Edition, in November in San Diego, and WonderCon, in April in Anaheim, Calif.

Both events also required that attendees wear masks.

The San Diego Convention Center, where the event is being held, reopened in August, and since then, it has held more than 90 events. Masks were required at some of those and recommended at others, or attendees were required to provide proof of vaccination or a negative coronavirus test, according to Maren Dougherty, a spokeswoman for the center.

Comic-Con, she added, is by far the largest event the center will hold since its reopening. In 2019, the event brought about $150 million into the local economy, Ms. Dougherty said. After several years without large events, she said, those attending events at the center have been largely respectful of protocols.

Plus, “masking has always been part of Comic-Con,” she added. “People have fun with that.”